Localization of bFGF in human transplant coronary atherosclerosis.
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Arteriosclerosis↗
Biomedical subjects
D Gordon
Publications and source records attributed to D Gordon.
Monocyte chemoattractant protein-1 in human atheromatous plaques.
Monocytes appear to be central to atherogenesis both as the progenitors of foam cells and as a potential source of growth factors mediating intimal hyperplasia, but the chemical messages which stimulate the influx of monocytes into human atheroma remain unknown. Monocyte chemoattractant protein-1 (MCP-1) is a recently described molecule with powerful monocyte chemotactic activity expressed by monocytes, vascular endothelial cells, and smooth muscle cells in culture. To begin to address the role of MCP-1 in vivo, we examined 10 normal arteries and 14 diseased human arteries for MCP-1 expression by in situ hybridization. MCP-1 mRNA was detected in 16% of 10,768 cells counted in human carotid endarterectomy specimens with highest expression seen in organizing thrombi (33%) and in macrophage rich areas bordering the necrotic lipid core (24%) as compared to the fibrous cap (8%) and the necrotic lipid core itself (5%). Based on immunohistochemical staining of serial sections and on cell morphology, MCP-1 mRNA appeared to be expressed by vascular smooth muscle cells (VSMC), mesenchymal appearing intimal cells (MICs), and macrophages. By contrast, few cells expressing MCP-1 mRNA were found in normal arteries (less than 0.1%). These data suggest a potential role for MCP-1 in mediating monocytic infiltration of the artery wall.
Arteriosclerosis↗
Growth and cell viability of aortic versus pulmonic homografts in the systemic circulation.
Growth characteristics and cell viability of aortic and pulmonic valve homografts in the systemic circulation were compared in a growing sheep model. Seven aortic and seven pulmonic cryopreserved homografts were implanted in the descending aortae of recipient female lambs. Of seven sheep per group, three were killed at 8 months, three at 12 months, and one at 15 months. Tissue cultures were obtained on homograft valve and root wall specimens. Male donor cells were identified by chromosome analysis. Preimplant to explant changes in pulmonic homograft external diameters at the valve annulus and sinotubular junction increased significantly more than in aortic roots. The postoperative dimensions of the distal anastomotic diameter and length of the graft increased significantly more in pulmonic than in aortic roots by time of explant. Leaflet calcification and valvular stenosis did not develop in either pulmonic or aortic homografts over the period of observation. Calcification in the root wall was significantly less in pulmonic than aortic homografts. Growth on tissue culture was obtained from over 70% of homograft specimens. Viable donor cells were demonstrated in none and 43% of aortic and pulmonic leaflets, respectively, and 71% and 57% of aortic and pulmonary arterial homograft walls, respectively. In conclusion, both aortic and pulmonic homograft valves provide freedom from calcification and stenosis in this model. Continuing expansion of pulmonic root diameters under systemic pressure might lead to late aneurysm formation. Although host cell repopulation of grafts may be advantageous, the presence of viable donor cells in leaflet tissue does not seem necessary to prevent calcific degeneration.
Animals↗
Advanced maternal age as a risk factor for cesarean delivery.
The rate of delivery by cesarean has increased steadily in the United States since the 1970s. The reasons for this increase are not fully established. Improved diagnosis of maternal and fetal complications, medicolegal concerns, and the changing age composition of childbearing women have been cited as contributing factors. To assess whether advanced maternal age by itself is an indicator for a primary cesarean delivery, we analyzed data from the vital records of all female residents of King County, Washington 35 years and older (N = 2985) who had a live singleton birth in 1986 or 1987. These women were compared with a sample of women 20-29 years old (N = 6140) who gave birth in the same time period and geographic area. Primiparous and multiparous women 35 years and older were at a similar increased risk of cesarean (relative risk = 1.6, 95% confidence interval 1.1-2.4). Primiparous women of all ages experienced more complications of pregnancy and labor and higher cesarean delivery rates. However, among primiparous mothers with no recorded complications, older women were at significantly increased risk of cesarean birth (relative risk = 2.5, 95% confidence interval 1.8-3.5). This analysis suggests that advanced maternal age alone may influence a physician's decision regarding method of delivery, thereby placing some older women at an unnecessary risk of cesarean.
Adult↗
Sodium channel polypeptides in central nervous systems of various insects identified with site directed antibodies.
Immunoprecipitation, radiophosphorylation and SDS-PAGE autoradiography enable the characterization of sodium channel polypeptides in the central nervous system of insects belonging to four phylogenetically distinct orders: grasshoppers, cockroaches, flies and moth larvae. It has been shown that the insect sodium channels: (1) Are recognized by the previously described (Gordon et al. (1988) Biochemistry 27, 7032-7038) site directed antibodies corresponding to a highly conserved segment linking the homologous domains III and IV in the vertebrate sodium channel alpha subunits. (2) Serve as substrates for phosphorylation by cAMP-dependent protein kinase. (3) Are devoid of disulfide linkage to smaller subunits unlike sodium channels in vertebrate brain. (4) Are glycoproteins as shown in the grasshopper by the decrease of apparent molecular weight following endoglycosidase F treatment and specific binding to the lectins concanavalin A and wheat germ agglutinin. (5) Reveal a diversity with regard to their (a) apparent molecular masses which range from 240 to 280 kDa and (b) V8 proteinase digestion phosphopeptides indicating either differences in the positioning of the enzymatic cleavage and/or phosphorylation sites. These results provide the first evidence for structural diversity of sodium channel subtypes among various insect orders and are compared to their mammalian counterparts.
Amino Acid Sequence↗
Proliferative retinopathy with growth hormone deficiency and diabetes mellitus.
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Diabetic Retinopathy↗
Sleep patterns in borderline personality disorder.
Sleep patterns of borderline patients with and without a history of affective disorder were compared to each other and to normal reference data. The three groups could not be distinguished in terms of REM latency because a wide spread of values was seen within each group. Borderlines were different from normal controls in other aspects of sleep architecture; they had less total sleep, more stage 1 sleep, and less stage 4 sleep. If one assumes that REM latency is a biological marker for mood disorder, then our results do not support the hypothesis that borderline personality disorder is a variant of affective illness. However, other data suggest that REM latency should not be used to validate the presence of affective illness.
Adult↗
Ion channels in nerve and muscle cells.
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Animals↗
Mechanism of long-term degeneration of arterialized vein grafts.
This study examined long-term changes in the morphology and cellular kinetics of rabbit vein grafts transplanted into the carotid artery. Six grafts were studied 1 year after implantation. Although the circumference and thickness of the wall were not different than at 12 weeks, degenerative changes occurred. The endothelial lining of the graft appeared intact, but large segments of the graft surface no longer excluded Evans blue dye, suggesting increased permeability. Collections of red blood cells were noted within the intima. Several grafts had extensive subendothelial fibrin deposits, often associated with foam cells, and evidence of previous hemorrhage, but these changes did not stimulate significant smooth muscle cell proliferation. Increased permeability with entrance of proteins and erythrocytes into the intima may result from increased wall tension or from low shear rates at the wall. Similar changes may lead to atherosclerosis in human vein grafts at late times.
Animals↗
Time-course and relationship of the early changes in renal sodium excretion and aldosterone secretion during dietary sodium restriction in normal man.
1. The fall in renal sodium excretion after dietary sodium restriction is prompt and reproducible. The importance of increased aldosterone secretion during the early phase (within 48 h) of this response is unclear. Using two indirect measures of aldosterone secretion (in urine and saliva), we have tried to relate changes in excretion and concentration of this hormone to renal sodium excretion during the abrupt transition from a normal (approximately 150 mmol/day) or high (260 mmol/day) to a low (5-25 mmol/day) sodium intake in 11 and seven male volunteers, respectively. 2. All subjects showed reduced renal sodium excretion within 36 h of dietary restriction, but the times at which increases in renal aldosterone excretion, saliva aldosterone concentration and plasma renin activity became statistically significant varied widely (8-72 h, 2.5- greater than 62.5 h and less than 4- greater than 38 h for renal aldosterone secretion, saliva aldosterone concentration and plasma renin activity, respectively). Circadian fluctuations in saliva aldosterone concentration were apparent and increased in amplitude during sodium restriction. 3. Urine flow rate tended to increase on the first day of sodium restriction and this reached statistical significance in the group initially on a high sodium intake (64.0 +/- 8.8 to 84.3 +/- 11.2 ml/h, P less than 0.01); although the pattern of urine flow did correlate with plasma arginine vasopressin concentration (r = -0.49, P less than 0.01), there was no significant decrease in mean plasma arginine vasopressin concentration [1.15 (0.92-1.44) to 0.90 (0.72-1.12) pmol/l, P = 0.08; geometric mean and 95% confidence limits].(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Cell proliferation in human coronary arteries.
Despite the lack of direct evidence for cell multiplication, proliferation of smooth muscle cells in human atherosclerotic lesions has been assumed to play a central role in ontogeny of the plaque. We used antibodies to cell cycle-related proteins on tissue sections of human arteries and coronary atherosclerotic plaques. Specific cell types were identified by immunochemical reagents for smooth muscle, monocyte-macrophages, and other blood cells. Low rates of smooth muscle cell proliferation were observed. Macrophages were also observed with rates of proliferation comparable to that of the smooth muscle. Additional replicating cells could not be defined as belonging to specific cell types with the reagents used in this study. These findings imply that smooth muscle replication in advanced plaques is indolent and raise the possibility of a role for proliferating leukocytes.
Animals↗
An assessment of the accuracy of NovoPen 1 delivery after prolonged use.
Forty-five NovoPen 1 injection devices have been assessed for accuracy of insulin delivery. Twenty-six pen-injectors had been returned either because the device had developed structural faults or the patients had experienced unexpected deterioration in diabetic control. Twelve of these pen-injectors were unusable. The remaining 14 pen-injectors ('faculty pen-injectors') were assessed by measuring the weight of insulin solution delivered in each of 10 depressions of the plunger and compared with similar measurements from 10 unused pen-injectors ('new pen-injectors') and 9 pen-injectors ('used pen-injectors') which had been used uneventfully for greater than 3 years. New pen-injectors delivered insulin solution with an accuracy (median error) of 2.8% and reproducibility (median SD) of 2.0%. Used pen-injectors had an accuracy of 2.3% and reproducibility of 3.5%. The 14 suspect pen-injectors ('faculty pen-injectors') demonstrated an accuracy of 2.8% with reproducibility of 4.0%. The reduction in reproducibility was due to faults in 4 pen-injectors, 2 of which consistently delivered less insulin than expected, while a further two pen-injectors were intermittently inaccurate.
Humans↗
Immunophenotype of vascular rejection in renal transplants.
Understanding of the pathogenesis of vascular rejection processes encountered in renal transplants is limited. Although initially and still widely thought to be antibody mediated, it is commonly difficult to demonstrate deposition of immunoglobulin (Ig) in affected arteries. We studied the vascular lesions present in 22 transplanted human kidneys with a panel of antibodies and lectins to evaluate the presence of granulocytes (Leu M1), leukocytes (anti-CD45), B cells (L26), T cells (UCHL-1), monocyte/macrophages (HAM 56), endothelial proliferation (Ulex I factor VIII-related antigen), and smooth muscle proliferation (HHF 35). Active (cellular) vascular rejection showed intimal infiltration of T lymphocytes and monocytes/macrophages (Mac) but not B lymphocytes. Lesions of greater chronicity (reduction in cellularity, increase in intimal stromal matrix) showed progressive diminution of the T cell infiltrate but persistence of Mac accompanied by increased smooth muscle cells. Endothelial alterations were limited to disruption and lifting from supporting stroma by infiltrating inflammatory cells; proliferative changes as detected by increased numbers of cells binding Ulex I were not identified. The cell infiltrates were similar in large (renal artery) and small (interlobular) arteries. Evidence for specific deposition of Ig was not present in cases studied by immunofluorescence studies. These studies suggest vascular rejection is commonly mediated by cellular immune mechanisms and the general supposition equating vascular rejection occurring beyond the peritransplant period with humoral rejection is mistaken. Persistent Mac in chronic lesions may be limited to scavenger functions, but their presence suggests activity in modulating intimal proliferation analogous to current hypotheses for such a role for Mac in atherosclerosis.
Arteries↗
An evaluation of human chorionic gonadotrophin (HCG) therapy in boys with delayed puberty.
Fifty male patients with delayed pubertal development (chronological age 13.3-17.6 years; bone age 9.5-14 years) were treated with human chorionic gonadotrophin (HCG) 1500-2000 units twice weekly for six months to promote pubertal development and accelerate growth. Response was compared with an untreated control group of 28 patients (chronological age 12.5-17.5 years; bone age 7.0-13.0 years). Forty-four of 46 patients in the treatment group achieved genital stage 3 or 4 by the end of therapy; untreated patients either remained unchanged or advanced only one genital stage during this period. Testicular volumes increased from a median 4.5 ml (range 1-12 ml) to 9 ml (range 3.5-15 ml) in the treated patients. In untreated patients testicular volume increased from 6.0 ml (range 2-10 ml) to 9.5 ml (range 4-20 ml) over the same period. In patients initially growing at less than 7.0 cm/year height velocity increased from 3.9 cm/year (range 0-6.6 cm/year) to 12.7 cm/year (range 8.9-16.8 cm/year) during therapy, falling to 6.0 cm/year (range 0-12 cm/year) in the three-month period immediately following treatment. Patients initially growing at greater than 7.0 cm/year showed variable responses to treatment. Prepubertal patients showed the greatest acceleration in annual growth compared with controls. Treated patients with an initial skeletal age less than 12.0 years showed either a final height (when known) which was less than initially predicted or a significant reduction in predicted height following treatment. Skeletal age greater than 12.0 years was not associated with excess osseous maturation. In conclusion, pre-pubertal children growing at less than 7 cm/year show the greatest benefit from HCG therapy, but final height may be prejudiced if initial bone age is less than 12 years.
Adolescent↗
Holy communion wafers and celiac disease.
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Catholicism↗
Comparison of ultrasound and lateral chain urethrocystography in the determination of bladder neck descent.
Several methods exist to determine the position of the bladder neck, an important mechanism of urinary continence. Radiologic screening is widespread but involves irradiation and may be imprecise. We compared perineal ultrasound scanning and radiologic scanning of the bladder neck by use of a chain and catheter and found good correlation between the two techniques. Ultrasound scanning is preferred, as it avoids irradiation, is accurate, is portable, and is readily available in most gynecologic departments.
Catheterization↗
Studies of intestinal lymphoid tissue. XII. Epithelial lymphocyte and mucosal responses to rectal gluten challenge in celiac sprue.
The immunopathologic, structural, and functional changes within rectal mucosa of known celiac sprue subjects were quantitated during local challenge with a peptic-tryptic digest of gluten. In the celiac sprue patients challenged with 2 g of digest, major effects occurred in lamina propria, submucosa, and local microvasculature. The lamina propria swelling was biphasic, starting 1-2 h after challenge with widespread extravascular deposition of fibrinogen, indicative of increased microvascular permeability, receding by 24 h postchallenge. A rapid fall in mast cells together with granule discharge suggested their involvement in this response. The late-phase swelling (48-72 h) was preceded by a rapid influx of neutrophils and basophils, the latter showing evidence of degranulation beyond 72 h. Reestablishment of vessel lumina, a rise in mast cells, and loss of neutrophils indicated tapering of the inflammatory cellular cascade by 96 h. Lymphocytes, first seen to enter the lamina by 2 h postchallenge, increased progressively, thereby resulting in substantial infiltration between 36 and 96 h. A marked rise in epithelial lymphocytes, maximal at 6-8 h, waned by 24 h. Volumes of surface and crypt epithelium remained constant throughout. In another challenge series with 4 g of gluten digest, electrical potential difference across rectal mucosa decreased significantly 12 h postchallenge, but the associated decreases in net sodium and chloride absorptive fluxes were insignificant. It is concluded that rectal mucosa is sensitized to gluten in celiac sprue disease and thus offers a promising and convenient in vivo substrate for investigative and diagnostic purposes.
Adult↗
Asymptomatic bacteriuria in normal and high-risk pregnancy.
A routine urine culture was performed in 1130 normal pregnant women and in 211 high-risk pregnancies (136 diabetics and 75 women with a previous urinary tract infection). Asymptomatic bacteriuria was found in 5.9% of the normal pregnancies, 12.5% among the diabetics and in 18.5% of the previous urinary tract infection patients. The higher incidence of a clinical urinary tract infection among patients with asymptomatic bacteriuria was found statistically significant (p less than 0.001) in all three groups. A high correlation was found between a negative urine culture in early pregnancy and the absence of development of cystitis and pyelonephritis in later pregnancy. The incidence of asymptomatic bacteriuria in normal pregnant women who developed cystitis later in pregnancy was 33.3% and in those developing pyelonephritis, 66%. In the two high-risk pregnancy groups, the incidence of asymptomatic bacteriuria among those developing clinical infection was even higher, 58.3 and 85.7%, respectively, among the diabetics, and 60 and 66.6% respectively, among the previous urinary tract infection patients.
Bacteriuria↗